1.The Anti-Angiogenic Effect of Microbotox on Rosacea Is Due to the Suppressed Secretion of VEGF by Mast Cells Resulting From Internalization of the MRGPRX2 Receptor
Jing WAN ; Yue LE ; Meng-Meng GENG ; Bing-Qi DONG ; Zhi-Kai LIAO ; Lin-Xia LIU ; Tie-Chi LEI
Annals of Dermatology 2025;37(4):228-240
Background:
Intradermal microdroplet injections of botulinum toxin type-A (BoNT/A) effectively ameliorate rosacea-related angiogenesis, but the mechanism remains unclear.
Objective:
To explore the anti-angiogenesis of BoNT/A in the rosacea-like mouse model and to measure the secretion of vascular endothelial growth factor (VEGF) by mast cells.
Methods:
A rosacea-like mouse model was induced by LL37 in both Mas-related G-proteincoupled receptor B2 conditional knockout (MrgprB2 −/− ) mice and wild-type (WT) mice, then treated with BoNT/A and/or Apatinib. The abundance of endothelial cells and mast cells in mouse skin was determined using dual immunofluorescence staining. The VEGF levels in supernatants and cell lysates of laboratory of allergic disease 2 (LAD2) mast cells were assessed using reverse transcription quantitative polymerase chain reaction, western blots, and enzyme-linked immunosorbent assay. The effect of conditioned medium (CM) collected from LAD2 on human umbilical vein endothelial cells (HUVECs) was determined using tube formation assays. The number of proliferative cells was confirmed using the 5-ethynyl-2’-deoxyuridine incorporation assays.The effect of BoNT/A on the internalization of Mas-related G-protein-coupled receptor X2 (MRGPRX2) was detected using flow cytometry and immunofluorescence staining.
Results:
LL37-induced rosacea-like skin manifestations were significantly alleviated in MrgprB2 −/− mice compared to WT controls. BoNT/A mitigated the LL37-induced secretion of VEGF by LAD2. The CM from BoNT/A-treated LAD2 inhibited HUVEC proliferation and tube formation. The LAD2 cells co-treated with LL37 and BoNT/A exhibited dramatically enhanced MRGPRX2 internalization.
Conclusion
BoNT/A enhances LL37-mediated MRGPRX2 internalization in mast cells, thereby reducing VEGF secretion and neovascularization and improving facial flushing symptom in rosacea.
2.Analysis of risk factors and predictive efficacy for postoperative severe pulmonary infection in patients with severe traumatic brain injury
Yuxuan XIONG ; Zhi CAI ; Jin LIAO ; Fuchi ZHANG ; Kai ZHAO ; Hongquan NIU ; Kai SHU ; Ting LEI
Chinese Journal of Trauma 2024;40(5):405-410
Objective:To investigate the independent risk factors for postoperative severe pulmonary infection (SPI) in patients with severe traumatic brain injury (sTBI) and evaluate their predictive value.Methods:A retrospective cohort study was conducted to analyze the clinical data of 163 sTBI patients admitted to Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology from April 2021 and March 2023, including 101 males and 62 females, aged 20-80 years [53.0(46.0, 59.0)years]. The surgical procedures involved decompressive craniectomy, subdural hematoma removal, epidural hematoma removal, and intracranial hematoma removal. The patients were divided into SPI group ( n=62) and non-SPI group ( n=101) according to whether they had SPI postoperatively. The following data of the two groups were collected, including gender, age, preoperative Glasgow coma scale (GCS), elevated blood glucose, abnormal liver function, abnormal renal function, hemoglobin level, anemia, albumin level, hypoproteinemia, white blood cell count, neutrophil count, lymphocyte count, platelet count, neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI) and serum lactate dehydrogenase (LDH) level. All the hematological tests were performed on venous blood samples collected preoperatively before anti-inflammatory treatment. Independent risk factors for predicting the postoperative occurrence of SPI in sTBI patients were identified through univariate analysis and multivariable stepwise regression analysis. The predictive value of separate indicator or indicators combined was assessed by calculating the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Results:Univariate analysis demonstrated that preoperative GCS, albumin level, lymphocyte count, NLR, PNI and serum LDH level in both groups were significantly correlated with the postoperative occurrence of SPI ( P<0.05), while gender, age, elevated blood glucose, abnormal liver function, abnormal renal function, hemoglobin level, anemia, hypoproteinemia, white blood cell count, neutrophil count, platelet count, dNLR and PLR were not correlated with the postoperative occurrence of SPI in sTBI patients ( P>0.05). Multivariable stepwise regression analysis revealed that low lymphocyte count (95% CI -0.337, -0.013, P<0.05), high NLR (95% CI -0.023, -0.005, P<0.01), low PNI (95% CI 0.007, 0.026, P<0.01), and high serum LDH (95% CI -0.002, -0.001, P<0.01) were independent risk factors for SPI in sTBI patients ( P<0.05). ROC curve analysis indicated that low lymphocyte count, high NLR, low PNI and high serum LDH level could predict SPI in sTBI patients postoperatively, with the combination of PNI and serum LDH showing the highest predictive ability (AUC=0.78, 95% CI 0.70, 0.85). Conclusion:Low lymphocyte count, high NLR, low PNI, and high serum LDH level are independent risk factors for postoperative SPI in patients with sTBI, and the combination of PNI and serum LDH possesses a high predictive value for postoperative SPI in sTBI patients.
3.Observation and imaging analysis of signs of ankylosing spondylitis in spinal specimens
Wei-Xing ZHONG ; Zhi-Hong WANG ; Jun-Hua LI ; Li-Qing LIAO ; Zu-Jiang CHEN ; Yi-Kai LI
Acta Anatomica Sinica 2024;55(3):329-333
Objective To provide anatomical,radiological,and clinical diagnostic and therapeutic references for ankylosing spondylitis and spinal surgical operations.Methods Non-measurement spinal observations,X-ray examinations,and measurements were performed on two spinal specimens,along with digital image acquisition and processing.Results The first specimen included thoracic vertebra 7(T7)to lumbar vertebra 3(L3),with an average total length of 29.7 cm;the second specimen ranged from cervical vertebra 7(C7)to lumbar vertebra 2(L2),with an average total length of 38.3 cm.The specimens showed partial or complete calcification of ligaments,ossification of the small joints and intervertebral discs,and osteoporosis;The anterior-posterior diameter(width)of the vertebral foramen was narrower than that of a normal adult,while most of the superior-inferior diameter(height)was wider.Radiographically,the anterior longitudinal ligament calcification appeared as dot-like or striated,but it was actually flaky in the actual specimens.The specimens provided views of the facet joints,costovertebral joints,and intervertebral foramina that was difficult to demonstrate on two-dimensional X-ray images.Conclusion As ankylosing spondylitis progresses,the range of motion in spinal bending and rotation decreases,as does the extent of thoracic expansion,thereby affecting respiration and complicating procedures such as intraspinal anesthesia and sacral canal injections.In terms of diagnosis,bone specimens and X-ray films allow us to understand the development process and severity of ankylosing spondylitis more directly and accurately.
4.Clinical efficacy analysis of different materials for the repair of large frontal and temporal skull defects
Jin LIAO ; Zhi CAI ; Yu LI ; Jin LEI ; Kai ZHAO ; Hongquan NIU ; Kai SHU ; Ting LEI
Journal of Clinical Surgery 2024;32(8):811-813
Objective To investigate the clinical outcomes of cranioplasty with polyether ether ketone(PEEK)or titanium after large craniectomy in patients.Methods Clinical data of 150 patients undergoing skull repair due to large frontotemporal skull defect in our hospital from April 2018 to June 2022 were retrospectively analyzed,and they were divided into titanium mesh group and PEEK group according to different repair materials.The conditions of surgical site infection,bleeding,subcutaneous effusion,seizure,implant rupture or exposure in the two groups were compared.Results In the PEEK group,96.3%of patients needed to implant the repair material under the temporal muscle,which was significantly higher than that in the titanium mesh group(78.1%)(P<0.05).There were no significant differences in postoperative complications including infection,bleeding,seizure,implant rupture or leakage between the two groups(P>0.05).However,the incidence of postoperative subcutaneous effusion in PEEK group was higher than that in titanium mesh group(14.8%VS4.2%,P<0.05),and the difference was statistically significant.Conclusion Both titanium and PEEK can be used in cranioplasty for patients with large frontotemporal cranial defects.Subcutaneous effusion is common in patients underwent cranioplasty with PEEK postoperatively,which needs to be paid more attention.
5.Downregulation of MUC1 Inhibits Proliferation and Promotes Apoptosis by Inactivating NF-κB Signaling Pathway in Human Nasopharyngeal Carcinoma
Shou-Wu WU ; Shao-Kun LIN ; Zhong-Zhu NIAN ; Xin-Wen WANG ; Wei-Nian LIN ; Li-Ming ZHUANG ; Zhi-Sheng WU ; Zhi-Wei HUANG ; A-Min WANG ; Ni-Li GAO ; Jia-Wen CHEN ; Wen-Ting YUAN ; Kai-Xian LU ; Jun LIAO
Progress in Biochemistry and Biophysics 2024;51(9):2182-2193
ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.
6.Diagnosis and treatment status of perioperative anemia in patients with gastrointestinal neoplasms: a multi-center study in Hubei Province.
Peng ZHANG ; Cong Qing JIANG ; Zhi Guo XIONG ; Yong Bin ZHENG ; Ying Feng FU ; Xin Ming LI ; Dian Fu PANG ; Xiao Feng LIAO ; Xin TONG ; Huan Ming ZHU ; Zhen Hua YANG ; Guang Wei GONG ; Xiao Ping YIN ; Dong Liang LI ; Hong Jun LI ; Hong Liu CHEN ; Xue Feng JIANG ; Zhi Jun HE ; Yan Jun LU ; Xiao Ming SHUAI ; Jin Bo GAO ; Kai Lin CAI ; Kai Xiong TAO
Chinese Journal of Surgery 2022;60(1):32-38
Objective: To investigate the incidence and treatment of perioperative anemia in patients with gastrointestinal neoplasms in Hubei Province. Methods: The clinicopathological data of 7 474 patients with gastrointestinal neoplasms in 62 hospitals in 15 cities (state) of Hubei Province in 2019 were collected in the form of network database. There were 4 749 males and 2 725 females. The median age of the patients was 62 years (range: 17 to 96 years). The hemoglobin value of the first time in hospital and the first day after operation was used as the criterion of preoperative anemia and postoperative anemia. Anemia was defined as male hemoglobin <120 g/L and female hemoglobin <110.0 g/L, mild anemia as 90 to normal, moderate anemia as 60 to <90 g/L, severe anemia as <60 g/L. The t test and χ2 test were used for inter-group comparison. Results: The overall incidence of preoperative anemia was 38.60%(2 885/7 474), and the incidences of mild anemia, moderate anemia and severe anemia were 25.09%(1 875/7 474), 11.37%(850/7 474) and 2.14%(160/7 474), respectively. The overall incidence of postoperative anemia was 61.40%(4 589/7 474). The incidence of mild anemia, moderate anemia and severe anemia were 48.73%(3 642/7 474), 12.20%(912/7 474) and 0.47%(35/7 474), respectively. The proportion of preoperative anemia patients receiving treatment was 26.86% (775/2 885), and the proportion of postoperative anemia patients receiving treatment was 14.93% (685/4 589). The proportions of preoperative anemia patients in grade ⅢA, grade ⅢB, and grade ⅡA hospitals receiving treatment were 26.12% (649/2 485), 32.32% (85/263), and 29.93% (41/137), and the proportions of postoperative anemia patients receiving treatment were 14.61% (592/4 052), 22.05% (73/331), and 9.71% (20/206). The proportion of intraoperative blood transfusion (16.74% (483/2 885) vs. 3.05% (140/4 589), χ²=434.555, P<0.01) and the incidence of postoperative complications (17.78% (513/2 885) vs. 14.08% (646/4 589), χ²=18.553, P<0.01) in the preoperative anemia group were higher than those in the non-anemia group, and the postoperative hospital stay in the preoperative anemia group was longer than that in the non-anemia group ((14.1±7.3) days vs. (13.3±6.2) days, t=5.202, P<0.01). Conclusions: The incidence of perioperative anemia in patients with gastrointestinal neoplasms is high. Preoperative anemia can increase the demand for intraoperative blood transfusion and affect the short-term prognosis of patients. At present, the concept of standardized treatment of perioperative anemia among gastrointestinal surgeons in Hubei Province needs to be improved.
Adolescent
;
Adult
;
Aged
;
Aged, 80 and over
;
Anemia/epidemiology*
;
Blood Transfusion
;
Female
;
Gastrointestinal Neoplasms/surgery*
;
Humans
;
Length of Stay
;
Male
;
Middle Aged
;
Retrospective Studies
;
Treatment Outcome
;
Young Adult
7.Herbal textual research on Rubi Fructus.
Tian-Yue LIAO ; Zhi-Lai ZHAN ; Jin XU ; Kai-Yuan WANG ; Jing-Qiong WAN ; Yuan WEI ; Wu-Wei MENG ; Zhen OUYANG
China Journal of Chinese Materia Medica 2021;46(10):2607-2616
Rubi Fructus is a commonly used traditional Chinese medicine. The origin of Rubi Fructus is the dried fruit of Rubus chingii, a plant of the family Rosaceae, according to the 2015 edition of Chinese pharmacopoeia. There are some differences in the plant origin of Rubi Fructus in ancient herbal literature, to trace back its sources, we conducted a textual research on its origin, producing areas, quality evaluation, processing and concocting, properties, tastes and efficacy etc. based on the records of ancient herbal literatures and combined with plant morphology and related investigation. RESULTS:: showed that the variety of Rubi Fructus was more complex among ancient herbal literature, including R. coreanus, R. hirsutus, R. corchorifolius, R. foliolosus and other mixed varieties. Most scholars believe that the R. chingii has not been recorded in ancient herbal literature, while R. chingii was recorded as early as the Ming Dynasty in Compendium of materia medica through our textual research. Ancient Chinese herbs recorded that Rubi Fructus was mostly produced in Hubei, Shandong, Shanxi and Jiangsu provinces, while R. chingii mainly produced in Anhui, Jiangsu, Zhejiang, Jiangxi, Fujian and other provinces nowadays. Also, it was recorded that Rubi Fructus harvested in wheat field during May were the best. Besides, R. chingii with big, full, grain integrate, firm, yellow and green color, sour taste and impurity free possess the best quality in the contemporary. The ancient records of processing and concocting, properties, tastes and efficacy were basically the same as modern ones.These results provide the basis for the correct utilization and further development of Rubi Fructus.
China
;
Drugs, Chinese Herbal
;
Fruit
;
Humans
;
Materia Medica
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Medicine, Chinese Traditional
;
Rubus
8.Pro-pigmentary action of 5-fluorouracil through the stimulated secretion of CXCL12 by dermal fibroblasts.
Zhi-Kai LIAO ; Shuang-Hai HU ; Bin-Yu HAN ; Xie QIU ; Shan JIANG ; Tie-Chi LEI
Chinese Medical Journal 2021;134(20):2475-2482
BACKGROUND:
There is growing evidence that 5-fluorouracil (5-FU) combined with therapeutic trauma can effectively induce skin repigmentation in vitiligo patients who are unresponsive to conventional treatments. Previous studies have mainly focused on identifying the antimitotic activity of 5-FU for the treatment of skin cancer, but few studies have investigated its extra-genotoxic actions favoring melanocyte recruitment.
METHODS:
We utilized the full thickness excisional skin wound model in Dct-LacZ transgenic mice to dynamically assess the migration of melanocytes in the margins of wounds treated with or without 5-FU. The in-situ expression of CXCL12 was examined in the wound beds using immunofluorescence staining. Quantitative real-time polymerase chain reaction and Western blotting analyses were performed to detect the expression levels of CXCL12 mRNA and protein in primary mouse dermal fibroblasts treated with or without 5-FU. Transwell assays and fluorescein isothiocyanate (FITC)-phalloidin staining were used to observe cell migration and filamentous actin (F-actin) changes of melan-a murine melanocytes.
RESULTS:
Whole mount and cryosection X-gal staining showed that the cell numbers of LacZ-positive melanocytes were much higher in the margins of dorsal and tail skin wounds treated with 5-FU compared with the controls. Meanwhile, CXCL12 immunostaining was significantly increased in the dermal compartment of wounds treated with 5-FU (control vs. 5-FU, 22.47 ± 8.85 vs. 44.69 ± 5.97, P < 0.05). Moreover, 5-FU significantly upregulated the expression levels of CXCL12 mRNA (control vs. 5-FU, 1.00 ± 0.08 vs. 1.54 ± 0.06, P < 0.05) and protein (control vs. 5-FU, 1.00 ± 0.06 vs. 2.93 ± 0.10, P < 0.05) in cultured fibroblasts. Inhibition of the CXCL12/CXCR4 axis suppressed melanocyte migration in vitro using a CXCL12 small interfering RNA (siRNA) or a CXCR4 antagonist (AMD3100).
CONCLUSION
5-FU possesses a pro-pigmentary activity through activation of the CXCL12/CXCR4 axis to drive the chemotactic migration of melanocytes.
Animals
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Cell Movement
;
Cell Proliferation
;
Chemokine CXCL12/genetics*
;
Fibroblasts
;
Fluorouracil/therapeutic use*
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Humans
;
Mice
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RNA, Messenger
;
Receptors, CXCR4
9.Textual Research on Visci Herba
Jin XU ; Zhi-lai ZHAN ; Tian-yue LIAO ; Kai-yuan WANG ; Jing-qiong WAN ; Yuan WEI ; Zhen OUYANG
Chinese Journal of Experimental Traditional Medical Formulae 2021;27(15):124-131
Visci Herba, a commonly used Chinese medicinal, was often mistaken as Taxilli Herba in ancient Chinese materia medica. The two Chinese medicinals have often been confused even in present clinical practice, and their origins are difficult to be identified. Hence, it is necessary to carry out systematic and in-depth textual research. This paper explored the origin, producing area, quality evaluation, harvesting and processing, property, flavor, and efficacy of Visci Herba based on ancient Chinese materia medica of the past dynasties and modern plant morphology, so as to provide evidence for the development and utilization of Visci Herba. The findings demonstrated that Visci Herba was mostly recorded as Taxilli Herba until the name of Visci Herba appeared in the Tang Dynasty. The records of the two Chinese medicinals could be traced back to the Song Dynasty. Visci Herba and Taxilli Herba were officially listed as two different Chinese medicinals in the
10.Metabolic abnormalities associated with ketamine-associated bladder toxicity based on metabolomics
Zhi-gui WU ; Wen-xian YIN ; Hong-li LUO ; Yuan-kai SI ; Meng-qi SUN ; Lin-chuan LIAO
Acta Pharmaceutica Sinica 2020;55(8):1849-1854
The aim of the present study was to determine the metabolic changes and possible toxic mechanisms of ketamine-associated bladder toxicity. Twenty-four male Sprague-Dawley (SD) rats were randomly allocated into a control group, a low-dose group and a high-dose group. The behavior of these rats was observed every day. In addition, the weight, 2 h urinary frequency and organ coefficient of the bladder were measured. Serum IL-6 and TNF-

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